Abstracts 10e Wim Schellekens symposium 6 juni 2014
Marker-onderzoek bij de typering van het endometriumcarcinoom.
Dr. T. Bosse, Patholoog, LUMC.
De klassieke dualistische classificatie van het endometriumcarcinoom staat op het
punt om te worden aangescherpt door de recente bevindingen op het gebied van de
moleculaire pathologie. Sinds de jaren 80 is het dualistische model van Bokcman
omarmt, waarbij er 2 type epitheliale maligniteiten van het endometrium
onderscheiden worden. Deze tweedeling kan het biologische gedrag redelijk goed
voorspellen en de patholoog kan de 2 tumoren redelijk goed uitelkaar houden. De
type I tumoren zijn oestrogeen gedreven en hebben een indolent beloop, terwijl de
type II tumoren onafhankelijk zijn van oestrogenen en een meer agressief beloop
kennen. Om na chirurgie de aanvullende behandeling zo goed mogelijk af te
stemmen op de individuele patiënt wordt gebruik gemaakt van een risico-inschatting
die in hoge mate afhankelijk is van de pathologie beoordeling. De prognostische
tumorkenmerken (graad, diepte invasie, endocervicale betrokkenheid en LVSI) zijn
echter stuk voor stuk onderhevig aan forse interobservervariabiliteit en ondanks het
gebruik van deze criteria is er nog altijd sprake van over- en onderbehandeling. Met
de komst van nieuwe moleculaire technieken zijn wij in staat om de moleculaire
veranderingen die ten grondslag liggen aan deze tumoren in kaart te brengen.
Recent onderzoek van “The Cancer Genome Atlas (TCGA)” waarin 260
endometriumcarcinomen genetisch in kaart zijn gebracht laat een genetisch
landschap zien waarin tenminste 4 moleculaire subgroepen kunnen worden
onderscheiden met ieder een eigen prognose. Met de komst van deze “moleculaire
profielen” wordt de klassieke 2-deling dus aangescherpt en verder opgedeeld. Via
deze route komen we uit op een moleculaire indeling die niet afhankelijk is van de
subjectieve beoordeling van de patholoog en daarmee de reproduceerbaarheid kan
bevorderen. De kans is groot dat een dergelijk indeling het biologisch gedrag van het
endometriumcarcinoom beter kan voorspellen dan de huidige klassieke kenmerken.
Bovendien geeft deze indeling informatie die gebruikt kan worden om doelgerichte,
geïndividualiseerde therapieën te ontwikkelen. Tijdens mijn voordracht zal ik in gaan
op deze nieuwe ontwikkelingen en resultaten bespreken uit de onderzoeksgroep
gynecologische tumoren van de afdeling pathologie van het LUMC.
Assisted Hatching : het ei van Columbus?
Dr I. De Croo, Afdeling voor Reproductieve Geneeskunde, Universitair Ziekenhuis
Gent
Het proces waarbij het pré-implantatie embryo uit de zona pellucida treedt om te
kunnen implanteren wordt hatching genoemd. Het ‘hatchen’ van de blastocyst uit de
zona pellucida is een kritische stap in een opeenvolging van fysiologische processen
die leiden tot implantatie. Problemen bij het ‘hatchen’ uit de zona pellucida kunnen
aanleiding geven tot een verminderde implantatiekans. Een dikke zona en/of zona
pellucida verharding, te wijten aan in vitro cultuur condities, kunnen het natuurlijke
proces van hatching verstoren en leiden tot implantatie falen (Cohen et al., 1990).
Het artificieel openen van de zona pellucida is gekend als ‘assisted hatching’ (AH) en
wordt gebruikt als een methode om de implantatiecapaciteit van embryo’s te
verbeteren. Verschillende methoden werden reeds beschreven waaronder ‘zona
thinning’, ‘zona drilling’ en de volledige verwijdering van de zona pellucida. Hiervoor
kan gebruik gemaakt worden van chemische- mechanische- of lasertechnieken. In
1989 publiceerde Cohen et al. een hogere implantatiekans per embryo transfer na
partiële zona dissectie en concludeerde dat het openen van de zona pellucida het
hatching proces bevorderde. Hoewel veel onderzoekers het effect van AH sindsdien
hebben bestudeerd, blijft het gebruik van AH controversieel. Het blijft dus onduidelijk
of het gebruik van AH voor alle subgroepen van patiënten een voordeel kan
opleveren. Uit een recente meta-analyse (Martins et al., 2011) en Cochrane review
(Carney et al., 2012) werd geconcludeerd dat, bij een niet geselecteerde groep
patiënten, goede prognose patiënten of patiënten met verhoogde leeftijd AH, niet
leidt tot een betere klinische zwangerschapskans wanneer verse embryo’s worden
teruggeplaatst.
Referenties
Cohen J., Elsner C., Kort H., Malter H., Massey J., Mayer MP. Impairment of the
hatching process following IVF in the human and improvement of implantation by
assisting hatching using micromanipulation. Hum. Reprod. 1990; 5 :7-13
Cohen J., Malter H., Wright G., Kort H, Massey J, Mitchell D. Partial zona dissection
of human oocytes when failure of zona pellucida penetration is anticipated. Hum.
Reprod. 1989;4:435-42
Martins W, Rocha I, Ferriani R et al. Assisted hatching of human embryos: a
systematic review and meta-analysis of randomized controlled trials. Hum Reprod
Update 2011; 17: 438-453.
Carney S, Das S, Blake D et al. Assisted hatching on assisted conception (in vitro
fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Cochrane Database
Syst Rev 2012; 12:CD001894
Nanotechnologie en gezonde chips
Prof.dr. A. van den Berg, Universiteit Twente
Abstract niet ontvangen
Detecting fetal sub-chromosomal aberations in
maternal plasma at low costs.
Roy Straver, Marcel J.T. Reinders, Henne Holstege, Daphne van Beek,
Allerdien Visser, Cees B.M. Oudejans and Erik A. Sistermans
1. Introduction
Fetal genetic disorders can be detected during pregnancy by prenatal diagnosis
using Chorionic Villus Sampling, but the 1:100 chance to result in miscarriage
restricts the use to fetuses that are suspected to have an aberration. Detection
of trisomy 21 cases non-invasively is now possible due to the upswing of Next
Generation Sequencing (NGS) because a small percentage of fetal DNA is present in
maternal plasma. However, detecting other trisomies and smaller aberrations can
only be realized using high coverage NGS, making it too expensive for routine
practice.
2. Materials & Methods
We developed a method, WISECONDOR (WIthin-SamplE COpy Number aberration
DetectOR), which detects small aberrations using low coverage NGS. The increased
detection resolution was achieved by comparing read counts within the tested sample
of each genomic region with regions on other chromosomes that behave similarly in
control samples. This within-sample comparison avoids the need to re-sequence
control samples.
3. Results
WISECONDOR correctly identified all T13, T18, T21 and T22 cases (see figure 1)
while coverages were as low as 0.15 to 1.06. No false positives were identified.
Moreover, WISECONDOR also identified smaller aberrations, down to 20Mb, such as
del(13)(q12.3q14.3), +i(12)(p10) and i(18)(q10) (see figure 2).
The results show that any aberration >13Mb that we tested was correctly called,
whereas false positives were never >13 Mb. Even for the relatively small amount of
reads we used, this method provides nearly the same precision as karyotyping
would, for which detection of small aberrations is limited to 10Mb owing to the
resolution of imaging. As expected, chromosome 19 was more prone to false positive
results than other chromosomes, as it is known to have a different GC-content
compared to other chromosomes.
4. Discussion
Our work demonstrated that both chromosomal and subchromosomal aberrations
can be determined by withinsample comparison of bin read frequencies instead of
using a set of re-sequenced reference samples. WISECONDOR is able to detect
subchromosomal and chromososmal disorders at low sequencing coverage per
sample assuming it contains least 5% fetal DNA, with the exception of triploid
and mosaic cases. It thereby allows non-invasive prenatal diagnotiscs without
increasing costs compared to current practices for trisomy 21 detection
APC resistance and SHBG as markers of venous thrombosis during use of
hormonal contraceptives
Marjolein Raps1,2, Frans Helmerhorst3, Frits Rosendaal2, Huib van Vliet3,4
1
Department of Obstetrics and Gynaecology, MCH, Den Haag; 2 Department of
Clinical Epidemiology, LUMC, Leiden; 3 Department of Obstetrics and Gynaecology,
LUMC, Leiden; 4 Department of Obstetrics and Gynaecology, Catharina Hospital,
Eindhoven.
Introduction: The use of hormonal contraceptives is associated with a three- to
seven-fold increased risk of venous thrombosis. This risk depends on both the
estrogen dose and the progestogen type of combined oral contraceptives. Recently,
the oral contraceptive containing cyproterone acetate and ethinylestradiol (Diane-35
®) and the vaginal ring containing etonogestrel and ethinylestradiol (Nuvaring ®)
were of media attention because use of these contraceptives had led to a few lethal
cases of venous thrombosis. Both contraceptives are known to be associated with an
increased risk of venous thrombosis compared with the most used oral contraceptive
containing levonorgestrel and ethinylestradiol (Microgynon-30®).
The risk of venous thrombosis is preferably determined by large prospective trials,
but since venous thrombosis is a rare event, a clinical study is almost impossible due
to the required number of participants. The risk of venous thrombosis during
hormonal contraceptive use can also be determined by the use of markers, for
example the validated marker Activated Protein C resistance (APC resistance) and
the recommended marker Sex Hormone Binding Globulin (SHBG).
Materials and Methodes: We performed an observational study in Leiden and
collected 262 women who used different hormonal contraceptives: oral, intrauterine,
vaginal and transdermal. APC resistance and SHBG levels as markers for venous
thrombosis were measured at baseline and after 3 months of contraceptive use. The
results were compared with APC resistance and SHBG levels of non-users and with
relative risks for venous thrombosis during use of the different hormonal
contraceptives in the literature.
Results: Users of hormonal contraceptives with a high thrombotic risk, e.g. the oral
contraceptive containing ethinylestradiol and cyproterone acetate (Diane-35 ®) or
ethinylestradiol and drospirenone (Yasmin ®) had a higher APC resistance and
higher SHBG levels than users of contraceptives with a low thrombotic risk, e.g. the
oral contraceptive containing ethinylestradiol and levenorogrestrel (Microgynon-30
®). Users of the transdermal patch (Ortho-Evra ®) had the highest APC resistance
and SHBG levels and users of the hormonal intrauterine device (Mirena®) had the
lowest APC resistance and SHBG levels. SHBG levels and APC resistance were
correlated with each other, and with the relative risks according to the literature.
Conclusion: APC resistance and SHBG are reliable markers to estimate the risk of
venous thrombosis during use of hormonal contraceptives.
METABOLOMICS PROFILING FOR IDENTIFICATION OF NOVEL POTENTIAL
MARKERS IN EARLY PREDICTION OF PREECLAMPSIA
Sylwia Kuc1, Maria P.H. Koster1, Jeroen L.A. Pennings2, Thomas Hankemeier3,4,
Ruud Berger3,4, Amy C. Harms4, Adrie D. Dane4, Peter C.J.I. Schielen5, Gerard H.A.
Visser1, Rob J. Vreeken3,4
1. Department of Obstetrics, Wilhelmina Children’s Hospital, University Medical
Centre Utrecht (UMCU), Utrecht, the Netherlands
2. Laboratory for Health Protection Research (GBO), National Institute for Public
Health and the Environment (RIVM), Bilthoven, the Netherlands
3. Leiden Academic Center for Drug Research, Division of Analytical
Biosciences, Leiden University, Leiden, The Netherlands
4. The Netherlands Metabolomics Centre, Leiden University, Leiden, the
Netherlands
5. Laboratory for Infectious Diseases and Perinatal Screening (LIS), National
Institute for Public Health and the Environment (RIVM), Bilthoven, the
Netherlands
Corresponding author: Sylwia Kuc (MD, MSc). Department of Obstetrics, Wilhelmina
Children’s Hospital, University Medical Centre Utrecht UMC, KE.04.123.1, P.O. Box
85090, 3508 AB Utrecht, the Netherlands, tel. +31-88-7553923, e-mail:
S.Kuc@umcutrecht.nl, fax: +31-88-7555320
Objective:
To investigate if specific signatures of metabolic biomarkers significantly differ in the
first trimester serum of women who subsequently developed preeclampsia (PE)
compared to that of healthy controls. The performance of selected metabolites was
evaluated for use during the first trimester screening of PE.
Methods:
This was a case-control study of maternal serum samples collected between 8+0 and
13+6 weeks of gestation from 167 women who subsequently developed PE (early
onset PE [EO-PE] n = 68; late onset PE [LO-PE] n = 99) and 500 controls with
uncomplicated pregnancies. Metabolomics profiling analysis was performed using
two methods. One has been optimized to target eicosanoids/oxylipins, which are
known inflammation markers and the other targets compounds containing a primary
or secondary biogenic amine group. Logistic regression analyses were performed to
predict the development of PE using metabolites alone and in combination with first
trimester mean arterial pressure (MAP) measurements.
Results:
Two metabolites were significantly different between EO-PE and controls (taurine
and asparagine) and one in case of LO-PE (glycylglycine). Taurine appeared the
most discriminative biomarker and in combination with MAP predicted EO-PE with a
detection rate (DR) of 55%, at a false-positive rate (FPR) of 10%.
Conclusion:
Our findings suggest a potential role of taurine in both PE pathophysiology and first
trimester screening for EO-PE.
A positive NIPT result: does it indeed predict a fetus with a trisomy?
L.F. Johansson1, E.N. de Boer1, E.M.J. Boon2, R.F. Suijkerbuijk1, K. Bouman1, C.M.
Bilardo3, I.M. van Langen1, R.J. Sinke1, B. Sikkema-Raddatz1, G. J. te Meerman1
1Department
of Genetics, University of Groningen, University Medical Center
Groningen, Groningen, The Netherlands
2Department
of Clinical Genetics, Laboratory for Diagnostic Genome Analysis
(LDGA), Leiden University Medical Center, Leiden, The Netherlands
3Department
of Obstetrics and Gynaecology, University of Groningen, University
Medical Center Groningen, Groningen, The Netherlands
As of April 1st Non-Invasive Prenatal Testing (NIPT) will be offered to women in the
Netherlands with an increased risk of carrying a child with a trisomy 13, 18 or 21 after
the combination test. In the future, however, this test might be offered to all pregnant
women, regardless of their risk of carrying a child with a trisomy. Here, we
demonstrate what effect the test has on the predictive value of a positive NIPT result
when offering to all women.
In blood of a pregnant woman a small percentage cell free fetal DNA is
present which can be investigated using NIPT. In pregnancies with a trisomic fetus a
higher percentage of DNA will originate from the trisomic chromosome. To
differentiate between a disomic or trisomic (positive) result, a Z-score is calculated,
representing the number of standard deviations that the fraction of a chromosome
deviates from the expected fraction. In general a Z-score higher than three is
interpreted as trisomic, giving a specificity of 99,87%. Recent research has indicated
a sensitivity >99% in series with an increased number of trisomies and fetal
percentages above three percent. In this study we demonstrate that for the
interpretation of a positive NIPT result of an individual patient, in addition to the
specificity and sensitivity of the test also the positive predictive value (PPV) should be
calculated. The additional value of the PPV is that the individual a priori risk for the
specific trisomy is taken into account, demonstrating more clearly the individual
chance for a trisomic fetus after the test.
We created easy to read tables, showing the PPV related to the a priori risk of
a trisomy for an individual patient. The first can be used before the NIPT to determine
what the individual PPV would be in case of a positive result based on only the a
priori risk. The second table shows the relation between the fetal percentage and the
PPV. The third table shows the PPV after NIPT based on the calculated Z-score.
These tables show for instance that an a priori risk of 1:30 of a trisomy 21 and a Zscore of three, the PPV is 96%, meaning that in 4% of the positive cases the fetus
will not have a trisomy 21. For an a priori risk of 1:1000 however, the PPV drops to
43% , meaning that in 57% of pregnancies with a positive NIPT result, the fetus will
not have a trisomy 21.
Our calculations of the PPV can help professionals to better understand NIPT
results and the provided tables can be used as helpful tools in daily practice.
What can we know about the fetus by analyzing the mother’s blood: from sex
to whole genome
Prof. Dr..K.C.A. Chan, Department of Chemical Pathology, Faculty of Medicine
The Chinese University of Hong Kong
Prenatal diagnosis is an established part of modern obstetric care. In 1997, Professor
Dennis Lo demonstrated that chromosome Y sequences could be detected in the
cell-free plasma of pregnant women carrying male fetuses but not in those with a
female fetus. This discovery of the presence of fetal DNA in maternal plasma has led
us into the era of noninvasive prenatal testing. To date, noninvasive prenatal
diagnostic applications of a number of different fetal genetic disorders have been
developed. We have demonstrated that using massively sequencing of the maternal
plasma DNA, the aberration in chromosome 21 dosage can be sensitively detected in
pregnant women carrying Down syndrome fetuses. This method has been rapidly
adopted throughout the world and over half of million tests have been done globally
since the first clinical service started in 2010 in the USA. To illustrate the power of
this technology, we decoded the genome-wide genetic profile of a fetus noninvasive
by sequencing the maternal plasma DNA to a 65-fold genome coverage. We used
the genetic map of the parents as scaffolds to construct the fetal genetic map. To
demonstrate the clinical application of this approach, we accurately determined the
mutational status of the fetus for β-thalassemia as both parents were carriers of the
disease with different mutation. The capability of noninvasive profiling of the fetal
genome suggests that any inheritable disease can potentially be diagnosed
prenatally using maternal plasma analysis.
Circulating free DNA as a marker for cancer: a revolution for diagnosis and
therapy.
Stefan Sleijfer, Department of Medical Oncology, Erasmus MC Cancer Institute,
Rotterdam, The Netherlands.
In oncology we currently live in the era of precision medicine in which we try to
identify factors that drive the malignant behavior of tumor cells and we try to identify
drugs that inhibit the function of such factors. The identification of the importance of
estrogen receptor (ER) and the subsequent successes of hormonal agents targeting
ER in breast cancer underlined the great potential of this approach. This successful
example has been followed in the last decade by a constantly increasing list of tumor
cell related factors that guide treatment decision making in an expanding number of
tumor types. Most of these tumor-driving factors that can serve as treatment target
concern DNA mutations. Examples included HER2 amplification in breast and gastric
cancer, EGFR mutations and EML-ALK translocation in non-small cell lung
carcinoma, c-KIT mutations in gastro-intestinal stromal tumors, and BRAF mutations
in melanoma. And the advent of drugs inhibiting the function of these deregulated
genes has substantially improved the outcome for many patients.
However, apart from a few very exceptional cases, patients with cancer cannot be
cured due to drug resistance. Genomic instability is one of the main hallmarks of
cancer and causes that tumor cells constantly evolve. This eventually renders tumor
cells to become resistant against the drugs that they are exposed to by the
emergence of novel DNA mutations, which is clinically reflected by treatment failure.
Insight into the mechanisms that underlie resistance and whether these mechanisms
can serve as a treatment target is essential for further progress in oncology.
Because of the constantly changing molecular make-up of tumor cells and the
importance that has for patient management, we need tools to characterize
metastatic tumor cells before and repetitively during treatment. Since taking biopsies
from solid metastases is a painful and cumbersome procedure for patients and
frequently impossible given inaccessibility of metastases, for example in the case of
isolated brain metastases, assessing the characteristics of metastatic tumor cells by
isolation of circulating tumor cells (CTCs) or cell-free tumor DNA (ctDNA), so called
liquid biopsies, is very attractive.
In this presentation, an oversight will be provided on the promises that ctDNA and
characterization of CTCs bear for oncology.
Regulating the introduction of health care innovations from a legal perspective
Prof.dr.mr A.C. Hendriks en mr. drs. B. van der Kamp.
The rapid developments in the field of health care raise high expectations amongst
the general population and patients groups in particular. Once new forms of health
care (‘health care innovations’) – notably treatment methods, medical devices and
medicines – are reported to have positive effects, the need is felt to allow as many
people as possible to benefit from these goods and services. Health care innovations
can lead to more or enhanced ways to prevent or delay the manifestation of a
disease as well as assist individuals affected by health impairments in better
managing their life according to their own wishes. Giving the importance of good
health – however defined – for the quality of life and the possibilities to participate in
society, merely permitting – not prohibiting – access to health innovations often is not
always enough. Enabling those in greatest need to effectively benefit from health
care innovations may also require that measures are taken to guarantee their
financial accessibility, e.g. by including these goods and services in health care
insurance policies.
Such a welcoming approach towards health care innovations does not only respond
to a need felt by a large proportion of the population, but is seemingly also an
obligation under international human rights law. According to the internationally
recognised right to health, States are bound to promote public and individual health
and prevent disease and infirmity. On the basis of this right, States are under the
obligation to take all necessary legislative and other measures to achieve these
goals. It can be argued that States are therefore also under a legal requirement to
enable the rapid introduction of and access to promising health care innovations.
lt follows that the law should facilitate the introduction of health care innovations, and
ensure that these forms of treatment become accessible to everyone in need. The
rapid introduction of health care innovation is not only embedded in the right to health
but can also contribute to the realisation of goals enshrined in the right to life, the
prohibition of inhuman treatment and the right to self-determination.
On the basis of these and other human rights, States are however also obliged to
prevent the hasty introduction of new forms of health care, particularly in the absence
of scientific evidence about their precise effects and possible risks. In fact, States
should – when seeking to respect the right to privacy and self-determination – also
prevent people from becoming (over) exposed to (commercial) information
influencing their decision-making process when it comes to such issues as
consenting to subjecting oneself to a form of (innovating) treatment of not. Selfdetermination also entails the right not to know and to refuse forms of treatment.
This raises the question how to balance these potentially conflicting interests,
particularly taking into account the financial constraints of individuals and health care
systems.
In this presentation we will explore the precise meaning of the human rights involved
when it comes to regulating the introduction of health innovation. We will assess the
importance of the rights involved and seek to weigh them in a comprehensive way,
also examining criteria on the basis of which the introduction of health care
innovations – including their financial accessibility – should be decided upon. In doing
so we will distinguish between the potential beneficiaries of health care innovations
(notably the individuals involved) and those whose rights be affected or otherwise be
encroached upon by allowing individuals to access health innovations, including
children and unborn children.
NIPT: dynamics and ethics
Prof..Dr. Guido M.W.R. de Wert, MUMC
Technical limitations and costs have dictated prenatal screening strategies so far.
However, NIPT and further developments in sequencing may converge and allow for
fetal whole-genome sequencing and analysis (WGSA) early in pregnancy. What,
then, is the desirable, ethically sound, scope of future prenatal screening?
A key criterion for any screening is that the possible advantages clearly outweigh the
possible disadvantages (proportionality). The main advantage of fetal WGSA would
be that it optimally meets the aim of facilitating reproductive choice – at least in
theory. However, possible disadvantages to be included in the balancing of pros and
cons include the following:
- informed consent (as traditionally understood) for WGSA seems to be rather
difficult, if not impossible;
- in view of the multitude and different kinds of test results, prenatal WGSA may well
generate complex and burdensome reproductive choices;
- possible non-medical information might be used for ‘trivial’ selective reproduction
(fetal selection);
- the generation of information on fetal risks for late-onset disorders may violate the
future child’s right not to know (its ‘right to an open future’).
Obviously, these risks and disadvantages do not regard prenatal WGS per se – they
regard fetal whole genome analysis. The question, then, becomes as to whether
whole genome sequencing should be followed by targeted analysis (using filters),
and if so: what criteria should be used to define the filters – and who should decide?
It is to be expected that NIPT will not only be used to detect larger numbers of fetal
abnormalities that may motivate pregnant women (prospective parents) to terminate
pregnancy. NIPT may simultaneously be used to detect conditions relevant to good
pregnancy outcomes, i.e. conditions that may result in primary and/or secondary
prevention. This development may contribute to the blending of aims of prenatal
screening – and to confusion regarding its ethical guiding principles. In order to
prevent such confusion, tests having different aims should be offered separately
wherever possible.
The current state of Non Invasive Prenatal Testing ( NIPT) in the Netherlands
Prof. Dr D. Oepkes, hoogleraar Verloskunde LUMC.
Sinds 1 april 2014 wordt in Nederland aan zwangeren met een verhoogde kans op
een foetale trisomie de NIPT aangeboden. Dit staat voor Non-Invasieve Prenatale
Test.
Uit plasma van de zwangere worden fragmentjes cel-vrij DNA (van moeder en
foetus) gesequenced. Door het aantal fragmentjes passend op elk chromosoom te
tellen kan aanwezigheid van een foetus met een trisomie 21, 18 of 13 betrouwbaar
worden voorspeld.
De evaluatie van deze landelijke proef-implementatie wordt uitgevoerd door het NIPT
consortium, en heet het TRIDENT project. Verwacht wordt dat het aantal zwangeren
dat kiest voor een vlokkentest of vruchtwaterpunctie drastisch zal dalen.
In de voordracht wordt dit project besproken, alsmede de resultaten van de eerste
twee maanden.